
Determinants of Right Heart Remodeling in Patients With CTEPH or PAH
Chronic Thrombo-embolic Pulmonary Hypertension and Pulmonary Arterial HypertensionRight heart failure is the main cause of morbi-mortality in patients with pulmonary hypertension (PH), including patients of chronic thrombo-embolic pulmonary hypertension (CTEPH) or pulmonary arterial hypertension (PAH) etiologies. Endarterectomy is an effective treatment for patients with CTEPH to lower pulmonary pressure. Evidence of postoperative right heart remodeling are contrasted according to the studies and determinants of right heart failure are still unclear. Similarly, few evidence exists on right ventricular remodeling after bilateral lung transplantation for patients with pulmonary arterial hypertension (PAH). Recent evidence have supported the role of inflammation and immunity in the pathophysiology of PAH . While several cytokines have been shown to predict survival , little is known on the implication of inflammation and immunity in postoperative Right Ventricular failure in patients with PAH. • The specific translational goal of this current project is to elucidate the role of immune biomarkers in 6 months postoperative right heart adverse remodeling in patients with CTEPH or PAH. We speculate that selected immune biomarkers (such as CXCL9, interleukin -18 or interferon) and growth factors (such as HGF) are correlated with mid-term postoperative right heart failure. All consecutive adults with either CTEPH referred to our center for endarterectomy, or PAH referred for lung transplantation, will be included, aiming for 150 CTEPH and 50 PAH. After inclusion, patients will undergo assessment of right heart dimensions and function by cardiac magnetic resonance imaging (MRI, including 4-Dimensions blood flow sequences) and 2D and 3D trans-thoracic echocardiography (TTE), as well as immune panel analysis. All patients will undergo as part of routine care right heart catheterization within a week after TTE and MRI imaging. On the day of surgery, pulmonary pressure will be measured by right heart catheterization monitoring (as part of routine care) in order to estimate the drop of pressure and to adjust for the extent of endarterectomy for patients with CTEPH. TTE will also be performed on the day of surgery if possible. At 7 days post-endarterectomy or transplant, clinical outcomes will be collected and peripheral blood will be collected. Patients will be prospectively follow-up for 6 months. Death, need for reintervention, duration of vasopressor after surgery and number, duration and cause of readmission will be recorded. At 6 months after surgery, all survivors will undergo the same biological sampling, as well as an 4D MRI and a 2D and 3D TTE. Data of right heart catheterization at 6 months (as part of routine care) will be collected as well.

Primary Care Strategies to Reduce High Blood Pressure: A Cluster Randomized Trial in Rural Bangladesh,...
HypertensionBackground: High blood pressure (BP) is the leading attributable risk for cardiovascular disease (CVD). In rural South Asia, hypertension remains to be a significant public health issue with sub-optimal rates of case finding and management. The goal of the full-scale study is to evaluate the effectiveness and cost-effectiveness of multicomponent primary care strategies on lowering blood pressure among adults with hypertension in rural communities in Bangladesh, Pakistan, and Sri Lanka. Methods/Design: The mixed-methods, stratified cluster randomized controlled trial Intervention: The multi-component interventions (MCI) is comprised of all the following five components: 1) home health education (HHE) by government community health workers (CHWs), plus 2) blood pressure (BP) monitoring and stepped-up referral to a trained general practitioner (GP) using a checklist, plus 3) training public and private providers in management of hypertension and using a checklist, plus 4) designating hypertension triage counter and hypertension care coordinators in government clinics, plus 5) a financing model to compensate for additional health services and provide subsides to low income individuals with poorly controlled hypertension. Usual care: Will comprise existing services in the community without any additional training. Participants: The trial will be conducted on 2550 individuals aged 40 years or older with hypertension (systolic BP ≥ 140 mm Hg or diastolic BP≥ 90 mm Hg, or on antihypertensive therapy) in 30 rural communities of Bangladesh, Pakistan and Sri Lanka. Out of the 2550 individuals, 420 with poorly controlled BP (Systolic BP≥160 mmHg or Diastolic BP≥100 mmHg) will be selected, 14 from each community, to investigate the effect of MCI on results from ambulatory BP monitoring. Qualitative component: Stakeholders including policymakers, district managers, and community health workers, GPs, hypertensive individuals and family members in the identified clusters will be surveyed. Outcome: The primary outcome will be change in systolic BP from baseline to follow-up at 24 months post randomization. The cost effectiveness outcome is the incremental cost of MCI per unit reduction in BP over the two year time period and in terms of incremental cost per CVD DALYs averted.

Exercise Capacity and Quality of Life in Patients With PPH Receiving Short Term Oral L-Citrulline...
Idiopathic Pulmonary Arterial HypertensionEisenmenger SyndromeDue to vasodilatory properties of the NO, one of the therapeutic approaches for IPAH is oral use of nitric oxide precursors (10). Efficacy of L-arginine is well-documented in the current literature but there is paucity of data with regard to L-citrulline- malate. Hence, this study will evaluate therapeutic efficacy of L-citrulline- malate in two categories of patients with pulmonary hypertension (IPAH, and Eisenmeger syndrome). This randomized clinical trial utilizes 6-minute walk, pro BNP levels and the echocardiographic indexes an indicator of functional improvement of the patients.

Impact of Computerized Decision Support on Racial/Ethnic Disparities in Hypertension Outcomes
HypertensionIn response to the Finding Answers: Disparities Research for Change call for proposals by the Robert Wood Johnson Foundation, we were funded to evaluate the effectiveness of a planned computerized decision support (CDS) intervention aimed at medical providers to overcome clinical inertia when treating blood pressure for hypertensive patients. Based on prior evaluation of the Brigham and Women's Hospital (BWH) adult primary care clinics, we hypothesize that racial and ethnic differences in blood pressure outcomes are largely attributable in differences in providers' aggressiveness in managing patients with hypertension based on patients' race and ethnicity. Within our network of 14 hospital and community-based Brigham and Women's Hospital adult primary care clinics, we aim to determine if the use of CDS to remind to medical providers of poorly controlled hypertensive patients to intensify their hypertension therapy will improve overall rates of blood pressure control and reduce the previously documented racial and ethnic disparities in blood pressure outcomes among our hypertensive patient population. Clinics will first be stratified by location (hospital-based versus community-based) and within each strata will be randomized to either have their providers receive CDS for hypertensive patients whose most recent blood pressure was uncontrolled or to usual care for hypertensive patients. More specifically, we will evaluate our planned intervention by utilizing an 18 month cluster-randomized controlled trial to examine the effectiveness the CDS for intensification of hypertension therapy in: improving levels of blood pressure control, improving provider adherence with recommended changes in drug therapy, and reducing racial/ethnic disparities in the processes of hypertension care and outcomes among our patients receiving primary care for a diagnosis of hypertension.

Effectiveness of the Vasodilator Test With Revatio, Made in Patients With Acute Pulmonary Hypertension...
Pulmonary HypertensionThe main objective is to validate the safety and efficacy of intravenous and oral sildenafil in the acute vasodilator test in patients with persistence of, at least, moderate pulmonary hypertension after valvular surgery successfully, with a correct left ventricular function and no valvular disease hemodynamically significant.

The Effect of Providing Free Samples of Generic Cardiovascular Medications to Physicians
HypertensionHyperlipidemiaIn this randomized controlled trial, we will provide primary care physicians with free samples of highly effective generic cardiovascular medications. We will test whether this intervention will stimulate cost-effective prescribing, reducing drug costs and improving adherence to essential cardiovascular medications.

Development and Pilot-Testing of a Patient Self Management Approach for Hypertension Using Personal...
HypertensionThe project includes a systematic review to inform refinement of intervention components and a pilot RCT to determine the uptake, feasibility, and potential value of a hypertension self-management strategy using personal health records. The review follows generally acceptable systematic review and/or meta-analytic techniques; with specific attention devoted towards accessing information and effectiveness data from unpublished studies or reports within grey literature and contacting individuals with expertise in chronic disease management in primary care. Findings of the review will be used to expand/modify an existing intervention 'template' to yield an evidence-based strategy with potential to enhance self-management of hypertension in primary care. The pilot RCT will assess the utility of the multifaceted intervention, delivered in part via a secure patient-controlled personal electronic health record, compared with the usual family practice management, for patients with undiagnosed or uncontrolled elevated blood pressure. Patients who are hypertensive or identified as high risk are expected to benefit from the increased flexibility and autonomy of out-of-physician-office self-monitoring with self-management support. This initial evaluation will focus on the change in hypertension knowledge, patient self-efficacy, and patient engagement in self management activities after 3 months, in the intervention group compared to the control group; the feasibility and acceptability of the intervention to patients and providers; and the processes involved in linking the patient self-management experience back to the patient's health care providers to promote coordination of care. Secondary outcomes include change in blood pressure, number and content of interactions with providers, and changes in management, including antihypertensive medication.

The Effect of Sitagliptin on Hypertension, Arterial Stiffness, Oxidative Stress and Inflammation...
Diabetes MellitusArterial StiffnessRecently a new category of antihyperglycemic therapy aiming to modulate the incretin system has emerged. These drugs induce insulin secretion without inducing hypoglycemia. The effect of the incretin modulators drugs on hypertension, arterial stiffness, inflammation and oxidative stress parameters have not been fully investigated yet.GLP-1 analogue has been suggested to have an effect on endothelium and the development of hypertension. Nystrom et al have demonstrated that GLP-1 improves endothelial dysfunction in a small group of type 2 diabetes subjects, with coronary heart disease. We hypothesize that DPP-4 inhibitor will have an effect on hypertension and arterial stiffness by effect on the NO pathway.The aim of this study is to investigate the effect of two insulin inducers drugs, sulfonyl urea and DPP-4 inhibitor on 24 hours blood pressure monitoring, arterial stiffness, oxidative stress and inflammation.

The Pharmacokinetics of Nifedipine Controlled Release Tablets in Hypertensive Patients on Hemodialysis...
Hypertension on Chronic Maintenance HemodialysisThis is a prospective, open, non-randomized, non-controlled study. 20 patients with hypertension on chronic maintenance hemodialysis will be enrolled in the study. All patients had mild to moderate hypertension and are receiving antihypertensive agents. This study was designed to investigate effects of Adalat GITS on hemodialytic blood pressures in patients with chronic hemodialysis by using ABPM and measuring the drug plasma concentrations. For the purpose of investigating the influence of hemodialysis on the drug plasma concentration as well as its efficacy, it should be necessary to assign the subjects with the Adalat monotherapy. Since most patients in the hemodialysis center will be those who need and already receive combination therapy, it would be practical to start Adalat 60mg/day monotherapy to remain similar antihypertensive effect when discontinuing the previous treatment in this study population to be screened and enrolled. And taking into the consideration of clinical practice, few patients undergoing hemodialysis could be well controlled by low dose Adalat 30mg/day alone. So this study will evaluate the effect and safety of Adalat GITS 60mg/day alone and thereafter the influence of hemodialysis on the drug plasma concentration without any other possible drug interaction. The agents are given orally once a day at 08:00h and patients are followed for at least 4 weeks. After that,the patients whose blood pressure are well controlled by Adalat GITS 60mg/day by office blood pressure would be enrolled for further ABPM assessment and plasma concentration evaluation.

e-Pharmacovigilance II - Surveillance for Safety and Effectiveness - Calling for Earlier Detection...
DiabetesDepression2 moreSpecific Aim 1: To develop a patient-reported, EHR-integrated system to actively monitor the safety and effectiveness of treatment for patients taking FDA-approved medications for one of four common chronic conditions (diabetes, hypertension, insomnia, depression), with integrated management support by a pharmacist. Specific Aim 2: To measure the reach, effectiveness, adoption and implementation of this integrated module for adult primary care patients in the Brigham and Women's Primary Care Practice-Based Research Network.